Evidence of Tandem Repeat and Extra Thiol-groups Resulted in the Polymeric Formation of Bovine Haptoglobin: A Unique Structure of Hp 2-2 Phenotype

Lai, Yi An; Lai, I-Hsiang; Tseng, Chi Feng; Lee, James; Mao, Simon J.T.

doi:10.5483/bmbrep.2007.40.6.1028

Cited by 13 publications

(18 citation statements)

References 26 publications

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“…Native bovine Hp was isolated from the plasma using an anti-bovine Hp immunoaffinity column, followed by gel-permeation chromatography (Superose-12) on a HPLC system as previously described [15]. Mouse and rabbit polyclonal antibodies against bovine recombinant Hp or mouse monoclonal antibody (mAb; 2H12) against bovine native Hp were prepared in our laboratory according to previously established procedures [3, 15].…”

Section: Methodsmentioning

confidence: 99%

“…Transfection of Hp cDNA into Chinese hamster ovary cells protects them against oxidative stress [30]. Structurally, bovine Hp is unique possessing only the Hp 2-2 phenotype [14, 15] with a molecular weight ranged from 660 to 730 kDa [15] which is different from that of humans expressed as Hp 1-1, 2-1, or 2-2.…”

Section: Introductionmentioning

confidence: 99%

“…Bovine Hp, while not abundantly expressed in normal plasma, is considered to be one of the sensitive acute phase proteins during bacterial infections [15, 24]. Several studies indicate that its concentration increases dramatically in both plasma and milk during clinical mastitis of dairy cows [6, 8, 21].…”

Section: Introductionmentioning

confidence: 99%

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Neutrophils as one of the major haptoglobin sources in mastitis affected milk

Lai

Tsao²,

et al. 2008

Vet. Res.

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The antioxidant haptoglobin (Hp) is an acute-phase protein responsive to infectious and inflammatory diseases. Hp and somatic cell counts (SCC) are sharply elevated in bovine milk following intramammary administration of endotoxin or bacteria. However, the sources of milk Hp responsible for such increases are not fully understood. The purpose of this study was to define the source of milk Hp from dairy cows with naturally occurring mastitis. Quarter milk samples selected from 50 dairy cows were separated into four groups according to SCC as group A: < 100 (n = 19); B: 100–200 (n = 10); C: 201–500 (n = 10); and D: > 500 × 103 (n = 11) cells/mL. Our results reveal that milk Hp concentrations were correlated with SCC (r = 0.742; P < 0.01), and concentrations in group D were ~10-fold higher than in group A. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicates that the milk somatic cells from group D were not only capable of synthesizing Hp but could also markedly increase Hp mRNA expression. Western blot, immunocytochemistry, double confocal immunofluorescence, and Hp releasing experiments demonstrate that neutrophils were associated with the biosynthesis and release of Hp in milk. It further shows that Hp was significantly elevated in the epithelium of mammary gland tissue with mastitis and was also expressed in the cultured mammary epithelial cells. We propose that neutrophils and epithelial cells may play an essential role in elevating milk Hp in addition to previous suggestions that Hp may be derived from mammary tissues and circulation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neutrophils as one of the major haptoglobin sources in mastitis affected milk

Lai

Tsao²,

et al. 2008

Vet. Res.

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“…Analysis of the electrophoretic patterns of Hp-hemoglobin complexes has suggested that most of these Hps are similar to human Hp 1-1 [28]. Only the protein found in ruminants (cattle, sheep and goat) resembled polymeric forms of human Hp 2-2 [20], but whether they also possess a tandem repeat remains unexplored [25]. It is thought that humans originally had a single Hp 1-1 phenotype [29].…”

Section: Evolutionmentioning

confidence: 99%

“…A unique feature of the Hp 2 allele is that it is present only in humans and is not found in any primates, including New and Old World monkeys, chimpanzees and gorillas [17]. We have recently found that cattle also possess Hp 2 as the sole genotype [25]. It is likely that ruminants including deer, cattle, goat and sheep may all possess a sole Hp 2-type allele.…”

Section: Evolutionmentioning

confidence: 99%

A unique tetrameric structure of deer plasma haptoglobin – an evolutionary advantage in the Hp 2‐2 phenotype with homogeneous structure

et al. 2008

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Haptoglobin (Hp) is an acute-phase protein (responsive to infection and inflammation) that is present in the plasma of all mammals [1][2][3][4]. A recent study has found that Hp also exists in lower vertebrates (bony fish) but not in frog and chicken [5]. The most frequently reported biological functions of the protein are to capture released hemoglobin during excessive hemolysis [6] and to scavenge free radicals during oxidative Similar to blood types, human plasma haptoglobin (Hp) is classified into three phenotypes: Hp 1-1, 2-1 and 2-2. They are genetically inherited from two alleles Hp 1 and Hp 2 (represented in bold), but only the Hp 1-1 phenotype is found in almost all animal species. The Hp 2-2 protein consists of complicated large polymers cross-linked by a2-b subunits or (a2-b) n (where n ‡ 3, up to 12 or more), and is associated with the risk of the development of diabetic, cardiovascular and inflammatory diseases. In the present study, we found that deer plasma Hp mimics human Hp 2, containing a tandem repeat over the a-chain based on our cloned cDNA sequence. Interestingly, the isolated deer Hp is homogeneous and tetrameric, i.e. (a-b) 4 , although the locations of )SH groups (responsible for the formation of polymers) are exactly identical to that of human. Denaturation of deer Hp using 6 m urea under reducing conditions (143 mm b-mercaptoethanol), followed by renaturation, sustained the formation of (a-b) 4 , suggesting that the Hp tetramers are not randomly assembled. Interestingly, an a-chain monoclonal antibody (W1), known to recognize both human and deer a-chains, only binds to intact human Hp polymers, but not to deer Hp tetramers. This implies that the epitope of the deer a-chain is no longer exposed on the surface when Hp tetramers are formed. We propose that steric hindrance plays a major role in determining the polymeric formation in human and deer polymers. Phylogenetic and immunochemical analyses revealed that the Hp 2 allele of deer might have arisen at least 25 million years ago. A mechanism involved in forming Hp tetramers is proposed and discussed, and the possibility is raised that the evolved tetrameric structure of deer Hp might confer a physiological advantage.Abbreviations Hp, haptoglobin; b-ME, b-mercaptoethanol.

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How are Trypanosoma brucei receptors protected from host antibody‐mediated attack?

Banerjee,

Minshall,

Webb

et al. 2024

BioEssays

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Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long‐term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin‐hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.

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Evidence of Tandem Repeat and Extra Thiol-groups Resulted in the Polymeric Formation of Bovine Haptoglobin: A Unique Structure of Hp 2-2 Phenotype

Cited by 13 publications

References 26 publications

Neutrophils as one of the major haptoglobin sources in mastitis affected milk

Neutrophils as one of the major haptoglobin sources in mastitis affected milk

A unique tetrameric structure of deer plasma haptoglobin – an evolutionary advantage in the Hp 2‐2 phenotype with homogeneous structure

How are Trypanosoma brucei receptors protected from host antibody‐mediated attack?

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